The process of angiogenesis, or new blood vessel growth, may promote host defense and tissue repair or exacerbate disease conditions leading to organ dysfunction. In a number of pathologies, angiogenesis forms a strong reciprocal relationship with the process of inflammation. Recruited inflammatory cells facilitate neovascularization through the release of proangiogenic growth factors, including vascular endothelial growth factor. Newly formed blood vessels promote additional recruitment of inflammatory cells, thereby promoting the chronic aspect of inflammation. Various types of inflammatory cells, in particular of myeloid origin, are guided by and contribute to hyperoxidative conditions characterized by the presence of oxidized lipids and modified proteins.
Hyperoxidative conditions lead to the generation of a host of oxidative products, including hydroxy-ω-oxoalkenoic acids and their esters. When present in oxidized phospholipids, these molecules are recognized by scavenger receptor CD36 and contribute to atherosclerosis progression and platelet hyper-reactivity. Hydrolysis followed by reaction of the resulting unesterified hydroxy-ω-oxoalkenoic acids with proteins, or reaction of the esterified hydroxy-ω-oxoalkenoic acids with proteins followed by hydrolysis gives rise to a family of carboxyalkylpyrole protein adducts, among them 2-(ω-carboxyethyl)pyrrole adducts and similarly modified compounds. These adducts, which are present in oxidized LDL, can accumulate in atherosclerotic plaques. They are also found in the retina in photoreceptor outer segments and retinal pigmented endothelial cells, where they contribute to age-related macular degeneration progression, inter alia, by promoting choroidal neovascularization.